Cholangitis: what is it, symptoms, treatment, prognosis, complications

What is cholangitis?

Cholangitis is a life-threatening inflammation of the bile ducts that is caused by an ascending bacterial infection. Choledocholithiasis (presence of stones in the bile ducts) is the most common cause when causing infection stones in the common bile duct lead to partial or complete obstruction of the bile duct systems. Diagnosis is by clinical presentation, abnormal laboratory findings, and imaging tests suggesting infection and biliary obstruction.

Initial drug therapy is based on early infusion and appropriate antibiotics. Late treatment can lead to septic shock. Depending on the course and severity, the biliary drainage procedure can be performed using endoscopic and surgical means. Acute cholangitis is treatable with proper treatment. However, mortality can be quite high if treatment is delayed significantly. There are many types of cholangitis, including 

primary biliary cholangitis, IgG4-associated sclerosing cholangitis, and primary sclerosing cholangitis. The most common of these is acute bacterial cholangitis and will be the focus of this article.

Causes and risk factors

Acute cholangitis most often results from a bacterial infection of the bile ducts. For the development of acute cholangitis, obstruction of the biliary tract is required. Complete obstruction can lead to increased biliary pressure, often resulting in bacteremia. The most common reason obstruction of the biliary tract - choledocholithiasis. Other reasons include benign or malignant bile duct strictures, pancreas cancer, ampullar cancer or adenoma, tumors located in the gate of the liver, parasites (Clonorchis sinensis, Fasciola hepatica) affecting the common bile duct and gall bladder, roundworm (Ascaris lumbricoides), tapeworms (Taenia saginata), deposition of gallbladder due to obstruction of the biliary stent, blockage of gallstones in the neck of the gallbladder or gallbladder duct causing compression of the common bile or common hepatic duct, known as Mirizzi syndrome, periampullary diverticulum duodenumleading to a biliary obstruction known as Lemmel Syndrome and acquired immunodeficiency syndrome (AIDS).

The pathogens identified as causative agents of acute cholangitis are gram-negative and anaerobic organisms, the most common of which are Escherichia coli, Klebsiella, Enterobacter, Pseudomonas and Citrobacter. Iatrogenic administration of bacteria usually occurs after endoscopic retrograde cholangiopancreatography (ERCP) in individuals with biliary obstruction. The most important risk factors for acute cholangitis include increased triglyceride intake, a sedentary lifestyle, a body mass index (BMI) over 30, and rapid weight loss.

Symptoms and Signs

People with cholangitis complain of abdominal pain (especially in the right upper quadrant of the abdominal cavity), fever, chills, and feelings of discomfort (malaise). Some may report jaundice (yellowing of the skin and whites of the eyes).

Physical examination findings usually include jaundice and tenderness in the right hypochondrium. The Charcot triad is a set of three common signs of cholangitis: abdominal pain, jaundice, and fever. In the past, it has been assumed to be present in 50–70% of cases, although the frequency has recently been reported to be 15–20%. Reynolds' pentad includes a Charcot triad with the presence septic shock and confusion. This combination of symptoms indicates deterioration and development sepsis, and is even rarer.

In the elderly, symptoms may be atypical; they can directly collapse due to sepsis without showing any prior characteristic features. Patients with a permanent stent in the bile duct may not develop jaundice.

Epidemiology

Cholangitis is relatively rare. On average, fewer than 200,000 cases of acute cholangitis are reported annually. The average age of the sick is from 50 to 60 years. Men and women suffer the same. 6-9% of hospitalized patients with gallstone disease acute cholangitis is diagnosed. The prevalence of cholelithiasis varies among different ethnic groups. The disease is more common among Native Americans and Hispanics, less common among whites, and much less common among Asians and African Americans. In addition, people in Asia and countries with intestinal parasites, as well as black people with sickle cell anemia.

Pathophysiology

Acute cholangitis is a condition caused by acute inflammation and infection of the bile duct system, as well as an obstruction outflow of the biliary tract, which leads to an increase in the number of bacteria and endotoxins in the vascular and lymphatic drainage systems. Usually, when bile flows through the bile duct system, the bile duct epithelium secretes immunoglobulin A (IgA), which is an antiadhesive factor against bacteria to wash out ducts. However, when the intrabiliary pressure exceeds the bacteriostatic capacity of the biliary epithelium, it results in to increased inflammation and infection, leading to potentially fatal complications such as biliary sepsis and abscesses liver.

With regard to obstruction of the biliary tract, which is most often due to an underlying mechanical cholestasis such as choledocholithiasis, cholesterol stones the bile ducts are colonized by the biofilm of the bacterial pathogen and, when multiplied, are thought to produce inflammatory cytokines that cause mucosal obstruction shell. Primary bile duct stones are thought to be caused by the biliary infection itself, both of which lead to ascending infection throughout the biliary system.

Diagnostics

The diagnosis of cholangitis is characterized by clinical presentation, abnormal laboratory findings, and imaging tests suggesting infection and biliary obstruction. Laboratory tests for acute cholangitis include CBC, complete metabolic profile, liver function tests, reactive proteins, clotting profile, blood culture, urinalysis, blood group, screening and cross-matching, and level lipase. Leukocytosis with a predominance of neutrophils is a common finding, with leukopenia usually found in people with sepsis or immunocompromise. Liver function results are consistent with cholestasis, revealing hyperbilirubinemia and elevated alkaline phosphatase (ALP) and transverse gamma-glutamyl (PGG) levels.

The first method of choice is abdominal ultrasound. It is very sensitive and specific when examining the gallbladder and examining the expansion of the bile ducts. The classic sign of ascending cholangitis is thickening of the walls of the bile ducts, expansion bile ducts, including the common bile duct, as well as evidence of cholelithiasis and purulent material. This can help differentiate intrahepatic obstruction from extrahepatic obstruction. However, a normal abdominal sonogram does not necessarily rule out ascending cholangitis. Computed tomography of the abdomen (CT) can be performed as an adjunct to the study of comorbidities such as tumors liver/pancreas, metastases or liver abscess. Dilated intrahepatic and extrahepatic ducts and inflammation of the bile ducts can be evaluated. Another advantage is that computed tomography can help with differential diagnosis, including diverticulitis and pyelonephritis. One of the main disadvantages is that CT has a low sensitivity for diagnosing choledocholithiasis.

The most sensitive method for detecting common bile duct stones is magnetic resonance cholangiopancreatography (MRCP). MRCP is a non-invasive imaging test that can determine the cause and level of biliary obstruction, including choledocholithiasis, strictures, and biliary dilatation. ERCP is important for both diagnosis and treatment because it identifies the site of the obstruction and helps drain the biliary tract and obtain biopsy and culture samples from the bile duct systems. ERCP should be used in patients with high clinical suspicion and in those who benefit from therapeutic intervention.

Treatment

The goal of treating acute cholangitis is to eliminate both biliary tract infection and obstruction. The mainstay of treatment is antibiotic therapy aimed at intestinal pathogens and bile drainage. Emergency management includes assessment of airways, respiration, circulation, heart monitoring and pulse oximetry, obtaining intravenous access, providing aggressive fluid and electrolyte replacement, if necessary, and supportive therapy. Requires initiation of early intravenous antibiotics, which are known to reach high concentrations in the biliary tract, such as fluoroquinolones, extended-spectrum penicillins, carbapenems, and aminoglycosides. In more severe cases, adequate hemodynamic support, including vasopressors, may be required. Hospitalization is necessary for acute cholangitis, with mild and moderate severity - treatment is carried out in general medical departments, and with a severe form of the disease and signs of sepsis and hemodynamic instability - in intensive therapy.

In mild cases, most patients respond to drug therapy. Those who do not respond to drug therapy require immediate decompression. In severe patients with sepsis, treatment is immediate or urgent drainage of the biliary tract. Patients who show clinical improvement after drug therapy may have decompression before being discharged from the hospital. Decompression or drainage of the biliary tract can be achieved with ERCP, percutaneous transhepatic cholangiography (CCCG), drainage under the control of endoscopic ultrasonography (EUS) or surgical drainage. ERCP is the gold standard and method of choice for biliary decompression, as it is effective in 94-98% of cases. If bile duct stricture is present, a transpapillary biliary stent can be placed to drain the biliary tract. Due to the higher incidence of complications after surgery, the operation is intended for patients who have decompensated despite optimal treatment and endoscopic / percutaneous biliary drainage ways. Also useful in cases where hospital resources are limited in terms of imaging techniques and specialized services.

Forecast

In patients with mild forms of acute cholangitis, 80-90% of patients respond to drug therapy and have a good prognosis. People who have early signs of multiple organ failure, such as a change in mental status, renal failure, hemodynamic instability, as well as those who do not respond to conservative treatment and antibiotic treatment, should undergo emergency drainage of the biliary tract. Early drainage of the biliary tract results in faster clinical improvement and reduced mortality. The overall mortality rate after drainage of the biliary tract is less than 10%. However, the diagnosis can be missed in 25% of severe cases in patients with sepsis.

Without timely treatment, the mortality rate of such patients is 50%. The elderly with kidney failure, liver abscess, or malignant neoplasms are at high risk of death. The main cause of death of these people is multiple organ failure with septic shock. Causes of death in people who survive the initial stages of acute cholangitis include multiple organ failure, pneumonia and heart failure.

Complications

Complications include:

• liver abscess;
• spicy cholecystitis;
• portal vein thrombosis;
• acute biliary pancreatitis;
• liver failure;
• acute renal failure;
• bacteremia/sepsis;
• multiple organ failure.